18 April, 2017
...was one question asked on 15th March 2017 at the highly engaging Cambridge Science Festival panel discussion “Mini-me: How 3D organoids are revolutionising research”.
The scope of this question illustrates how excited people are about the innovative method of growing organs in a dish. Whilst the panel confirmed that scientist have successfully printed for example, heart organoids, (using a highly specialised 3D printer), it voiced a healthy scepticism about the possibility to create a large, fully functional organ with the currently available scientific methods. The sheer complexity of an organ – different cell types, connecting tissue, blood vessels and flow imposes limits on what is achievable at the moment.
Looking closer at the 3D-printed heart organoid, one will discover that these were about 0.25mm in size, so around 250 times smaller than a human heart. So, this is a great proof of concept and at the same time illustrates the long and challenging road towards applications in regenerative medicine such as creating tissues and organs suitable for transplantation. Most commonly organoids are grown in a mix of extracellular matrix proteins or so called ‘hydrogels’, which allow the cells to form 3D structures. Air also diffuses into these matrices to keep cells healthy. Naturally, there are limits to this gas diffusion process and panel members agreed that this is the main factor currently limiting the size of organoids.
Moving away from the 3D printer, already lots of exciting research using organoids is being conducted that will have a major impact on our understanding of the body in health and disease. I joined a panel with Emma Rawlins (Gurdon Institute), Joo-Hyeon Lee (Stem Cell Institute), Hayley Francies (Sanger Institute) to talk about our work with organoids, the potential and also the challenges of the technique.
Organoids as a 3D model system are a major step forward in comparison to classical 2D or polarised cell cultures. The latter ones consist of terminally differentiated cells which can divide for a limited number of times. In contrast, organoids contain stem cells which give rise to daughter cells that differentiate into the different cell types of the organ. This allows researchers to study basic biology, cancer and host pathogen interactions in an accessible system of organoids derived from mouse tissue or human patient/embryonic material.
The lung is the last organ to mature before birth and proper development is essential for survival of the newborn. Emma Rawlin’s group askes the question how stem cells develop the lung in the embryo and maintain it in adults. Along those lines, Joo-Heyon Lee’s group investigates how lung stem cells interact with their immediate environment in health and disease. Investigating the communication between cells in the lung is complex and relies on proper 3D organization of the cells. Innovations from tissue engineering, for example scaffolds made from novel biomaterials, can synergise with current methods to advance the model systems.
Cancer research is often restricted by limited availability of patient tissue for research. To overcome this barrier Hayley Francies and team have built an organoid biobank from patients with colorectal cancer. Establishing and propagating organoids from patient tumors allows them to identity so called biomarkers for the respective tumours and to develop novel cancer therapies.
I am part of a team at the Babraham Institute, that investigates how immune cells (intraepithelial lymphocytes) interact with the cells of the gut wall to protect the body from invading infectious agents. Intestinal organoids enable the researchers to study these interactions over a prolonged period for the first time. This finding opens up exciting possibilities for research on the interaction of immune cells and their environment at the intestinal epithelial barrier.
The discussion was followed by an informal get together. Different focus tables – ‘lung’, ‘cancer’ and ‘intestine’ - enabled members of the public to chat with scientists of various expertise. Marisa Stebegg and Joana Guedes from the Immunology programme at the Babraham Institute supported me at the ‘intestine’ table, discussing their research and experiences with intestinal organoids. It became very apparent that the therapeutic potential of the organoid system was of great interest to the public attendees, for example to treat diseases such as Inflammatory Bowel Disease (IBD). And whilst, clinical applications are on the horizon, the scientists also explained the importance of basic research as the groundwork for subsequent translational studies.
This engagement with a highly interested audience was an absolute delight and a great opportunity for researchers to shed light on a topic that is in the spotlight of public interest.
See you again at next year’s Cambridge Science Festival!
18 April 2017
By Guest Blogger